硫化氢通过激活Akt抑制铁死亡减轻ox-HDL诱导的人脐静脉内皮细胞功能障碍
R543%R363.2%Q255; 目的:探讨硫化氢(H2S)对氧化高密度脂蛋白(ox-HDL)诱导的人脐静脉内皮细胞(HUVECs)铁死亡及内皮细胞功能损伤的作用及机制.方法:体外培养HUVECs,用200 mg/L ox-HDL、铁死亡抑制剂ferrostatin-1(Fer-1)、蛋白激酶B(PKB/Akt)激动剂SC79、Akt抑制剂MK-2206 2HCl(MK)和/或H2S处理细胞24 h,Western blot检测相关蛋白,流式细胞术和免疫荧光染色检测细胞内活性氧(ROS)水平,铁离子检测试剂盒检测细胞内铁离子含量,单核细胞黏附实验检测单核细胞黏附到内皮细胞的数量.结果:与对照...
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| Published in | 中国病理生理杂志 Vol. 40; no. 6; pp. 961 - 970 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
南华大学衡阳医学院心血管疾病研究所,动脉硬化学湖南省重点实验室,动脉硬化性疾病湖南省国际科技创新合作基地,湖南 衡阳 421001
2024
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1000-4718 |
| DOI | 10.3969/j.issn.1000-4718.2024.06.001 |
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| Abstract | R543%R363.2%Q255; 目的:探讨硫化氢(H2S)对氧化高密度脂蛋白(ox-HDL)诱导的人脐静脉内皮细胞(HUVECs)铁死亡及内皮细胞功能损伤的作用及机制.方法:体外培养HUVECs,用200 mg/L ox-HDL、铁死亡抑制剂ferrostatin-1(Fer-1)、蛋白激酶B(PKB/Akt)激动剂SC79、Akt抑制剂MK-2206 2HCl(MK)和/或H2S处理细胞24 h,Western blot检测相关蛋白,流式细胞术和免疫荧光染色检测细胞内活性氧(ROS)水平,铁离子检测试剂盒检测细胞内铁离子含量,单核细胞黏附实验检测单核细胞黏附到内皮细胞的数量.结果:与对照组相比,ox-HDL组酰基辅酶A合成酶长链家族成员4(ACSL4)蛋白表达升高1.45倍(P<0.01),谷胱甘肽过氧化物酶4(GPX4)蛋白表达降低29.79%(P<0.05),ROS水平和铁离子含量分别升高4.81倍和1.40倍(P<0.01),p-PI3K/PI3K和p-Akt/Akt比值降低45.65%和41.68%(P<0.01),内皮细胞功能相关蛋白IL-6、ICAM-1和TNF-α表达分别升高1.18倍、1.24倍和1.41倍(P<0.05),内皮型一氧化氮合酶(eNOS)蛋白表达下降35.24%(P<0.01),与单核细胞的黏附作用升高3.43倍(P<0.01).与ox-HDL组相比,ox-HDL+H2S组内皮细胞铁死亡相关蛋白ACSL4降低22.32%(P<0.05),GPX4增加1.27倍(P<0.01),p-Akt/Akt比值增加1.52倍(P<0.01);荧光显微镜结果表明ROS表达降低50.35%(P<0.01);IL-6、ICAM-1和TNF-α蛋白表达分别降低13.34%、9.83%和13.46%(P<0.05),eNOS升高1.22倍(P<0.01),单核细胞黏附数量降低59.05%(P<0.01).与ox-HDL组相比,ox-HDL+SC79组GPX4蛋白表达升高1.49倍(P<0.01),ACSL4表达降低20.72%,ROS和铁离子含量分别降低59.31%和23.85%(P<0.05).与ox-HDL+H2S组相比,ox-HDL+H2S+MK组GPX4蛋白表达降低21.28%,ACSL4蛋白表达增加1.16倍(P<0.05).结论:H2S通过激活Akt抑制ox-HDL诱导的HUVECs铁 |
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| AbstractList | R543%R363.2%Q255; 目的:探讨硫化氢(H2S)对氧化高密度脂蛋白(ox-HDL)诱导的人脐静脉内皮细胞(HUVECs)铁死亡及内皮细胞功能损伤的作用及机制.方法:体外培养HUVECs,用200 mg/L ox-HDL、铁死亡抑制剂ferrostatin-1(Fer-1)、蛋白激酶B(PKB/Akt)激动剂SC79、Akt抑制剂MK-2206 2HCl(MK)和/或H2S处理细胞24 h,Western blot检测相关蛋白,流式细胞术和免疫荧光染色检测细胞内活性氧(ROS)水平,铁离子检测试剂盒检测细胞内铁离子含量,单核细胞黏附实验检测单核细胞黏附到内皮细胞的数量.结果:与对照组相比,ox-HDL组酰基辅酶A合成酶长链家族成员4(ACSL4)蛋白表达升高1.45倍(P<0.01),谷胱甘肽过氧化物酶4(GPX4)蛋白表达降低29.79%(P<0.05),ROS水平和铁离子含量分别升高4.81倍和1.40倍(P<0.01),p-PI3K/PI3K和p-Akt/Akt比值降低45.65%和41.68%(P<0.01),内皮细胞功能相关蛋白IL-6、ICAM-1和TNF-α表达分别升高1.18倍、1.24倍和1.41倍(P<0.05),内皮型一氧化氮合酶(eNOS)蛋白表达下降35.24%(P<0.01),与单核细胞的黏附作用升高3.43倍(P<0.01).与ox-HDL组相比,ox-HDL+H2S组内皮细胞铁死亡相关蛋白ACSL4降低22.32%(P<0.05),GPX4增加1.27倍(P<0.01),p-Akt/Akt比值增加1.52倍(P<0.01);荧光显微镜结果表明ROS表达降低50.35%(P<0.01);IL-6、ICAM-1和TNF-α蛋白表达分别降低13.34%、9.83%和13.46%(P<0.05),eNOS升高1.22倍(P<0.01),单核细胞黏附数量降低59.05%(P<0.01).与ox-HDL组相比,ox-HDL+SC79组GPX4蛋白表达升高1.49倍(P<0.01),ACSL4表达降低20.72%,ROS和铁离子含量分别降低59.31%和23.85%(P<0.05).与ox-HDL+H2S组相比,ox-HDL+H2S+MK组GPX4蛋白表达降低21.28%,ACSL4蛋白表达增加1.16倍(P<0.05).结论:H2S通过激活Akt抑制ox-HDL诱导的HUVECs铁 |
| Abstract_FL | AIM:To investigate the effect of hydrogen sulfide(H2S)on ferroptosis and functional impairment induced by oxidized high-density lipoprotein(ox-HDL)in human umbilical vein endothelial cells(HUVECs),and to ex-plore its mechanisms.METHODS:The HUVECs were cultured in vitro and exposed to 200 mg/L ox-HDL,ferroptosis in-hibitor ferrostatin-1(Fer-1),protein kinase B(PKB/Akt)inhibitor MK-2206 2HCl(MK),Akt agonist SC79,and/or H2S for 24 h.Western blot was used to identify the relevant proteins.Intracellular levels of reactive oxygen species(ROS)were analyzed by flow cytometry and immunofluorescence staining.Intracellular iron was measured using an iron detection kit.The number of monocytes adhering to endothelial cells was counted using the monocyte adhesion assay.RESULTS:Compared with control group,acyl-CoA synthetase long-chain family member 4(ACSL4)protein expression in ox-HDL group was elevated by 1.45-fold(P<0.01),glutathione peroxidase 4(GPX4)protein expression was decreased by 29.79%(P<0.05),and ROS levels and iron ion content were elevated by 4.81-fold and 1.40-fold,respectively(P<0.01).The ratios of p-PI3K/PI3K and p-Akt/Akt were decreased by 45.65%and 41.68%,respectively(P<0.01),endo-thelial cell function-related protein IL-6,ICAM-1 and TNF-α expression was elevated 1.18-fold,1.24-fold and 1.41-fold(P<0.05),respectively,eNOS protein expression was decreased by 35.24%(P<0.01),and monocyte adhesion was ele-vated 3.43-fold(P<0.01).Compared with ox-HDL group,the endothelial cell iron death-related protein ACSL4 was de-creased by 22.32%(P<0.05),GPX4 was increased by 1.27-fold(P<0.01),and the p-Akt/Akt ratio was increased by 1.52-fold(P<0.01)in ox-HDL+H2S group.The fluorescence microscopy results showed that the ROS was decreased by 50.35%(P<0.01).The IL-6,ICAM-1 and TNF-α protein expression was decreased by 13.34%,9.83%and 13.46%(P<0.05),respectively,eNOS was elevated by 1.22-fold(P<0.01),and the number of monocyte adhesion was de-creased by 59.05%(P<0.01).Compared with ox-HDL group,GPX4 protein expression in ox-HDL+SC79 group was ele-vated by 1.49-fold(P<0.01),ACSL4 expression was decreased by 20.72%(P<0.05),and ROS and iron ions were de-creased by 59.31%and 23.85%(P<0.05),respectively.Compared with ox-HDL+H2S group,GPX4 protein expression was decreased by 21.28%,and ACSL4 protein expression was increased by 1.16-fold in ox-HDL+H2S+MK group(P<0.05).CONCLUSION:H2S activates Akt to inhibit ox-HDL-induced ferroptosis in HUVECs and alleviate their func-tional damage. |
| Author | 吴泽凡 刘宁雅 王燕霞 姜志胜 易琪龙 |
| AuthorAffiliation | 南华大学衡阳医学院心血管疾病研究所,动脉硬化学湖南省重点实验室,动脉硬化性疾病湖南省国际科技创新合作基地,湖南 衡阳 421001 |
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| Author_FL | WU Zefan JIANG Zhisheng WANG Yanxia LIU Ningya YI Qilong |
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| Author_xml | – sequence: 1 fullname: 王燕霞 – sequence: 2 fullname: 吴泽凡 – sequence: 3 fullname: 易琪龙 – sequence: 4 fullname: 刘宁雅 – sequence: 5 fullname: 姜志胜 |
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| DocumentTitle_FL | Hydrogen sulfide attenuates ox-HDL-induced endothelial impairment by Akt-mediated inhibition of ferroptosis in HUVECs |
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| Keywords | human vascular endothelial cells oxidized high-density lipoprotein hydrogen sulfide 氧化高密度脂蛋白 硫化氢 人脐静脉内皮细胞 ferropto-sis 铁死亡 PI3K/Akt signaling pathway PI3K/Akt信号通路 |
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| Publisher | 南华大学衡阳医学院心血管疾病研究所,动脉硬化学湖南省重点实验室,动脉硬化性疾病湖南省国际科技创新合作基地,湖南 衡阳 421001 |
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| Title | 硫化氢通过激活Akt抑制铁死亡减轻ox-HDL诱导的人脐静脉内皮细胞功能障碍 |
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